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推进皮肤模型开发：聚焦于一种自组装、诱导多能干细胞衍生的无动物源方法。

Advancing skin model development: A focus on a self-assembled, induced pluripotent stem cell-derived, xeno-free approach.

作者信息

Dubau Marla, Tripetchr Tarada, Mahmoud Lava, Kral Vivian, Kleuser Burkhard

机构信息

Department of Pharmacology and Toxicology, Institute for Pharmacy, Freie Universität Berlin, Berlin, Germany.

出版信息

J Tissue Eng. 2024 Nov 5;15:20417314241291848. doi: 10.1177/20417314241291848. eCollection 2024 Jan-Dec.

DOI:10.1177/20417314241291848
PMID:39502328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536386/
Abstract

The demand for skin models as alternatives to animal testing has grown due to ethical concerns and the need for accurate substance evaluation. These alternatives, known as New Approach Methodologies (NAMs), are increasingly used for regulatory decisions. Current skin models from primary human cells often rely on bovine collagen, raising ethical issues. This study explores self-assembled skin models (SASM) as a new method, utilizing hair follicle-derived keratinocytes reprogrammed into induced pluripotent stem cells (iPSC) and differentiated into fibroblasts and keratinocytes. The model relies on the ability of fibroblasts to secrete collagen to produce a xeno-free dermal layer and on the differentiation of keratinocytes to create a functional epidermal layer. These layers exhibited confirmed metabolic activity and the capability to withstand test substances. The successful development of SASM underscores the significance of accurate alternatives in dermatological research, providing an ethical and reliable option for substance evaluation and regulatory testing.

摘要

由于伦理问题以及准确评估物质的需求，对作为动物试验替代方案的皮肤模型的需求不断增长。这些被称为新方法学（NAMs）的替代方案越来越多地用于监管决策。目前来自原代人类细胞的皮肤模型通常依赖牛胶原蛋白，引发了伦理问题。本研究探索了自组装皮肤模型（SASM）作为一种新方法，利用毛囊来源的角质形成细胞重编程为诱导多能干细胞（iPSC），并分化为成纤维细胞和角质形成细胞。该模型依赖于成纤维细胞分泌胶原蛋白以产生无动物源真皮层的能力，以及角质形成细胞的分化以形成功能性表皮层的能力。这些层表现出已确认的代谢活性和耐受测试物质的能力。SASM的成功开发凸显了准确替代方案在皮肤病学研究中的重要性，为物质评估和监管测试提供了一种符合伦理且可靠的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/2e1b993d993b/10.1177_20417314241291848-fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/56baa16110fe/10.1177_20417314241291848-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/a4ac5f8b4da3/10.1177_20417314241291848-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/29b64e2fecb0/10.1177_20417314241291848-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/bfae9172b94e/10.1177_20417314241291848-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/34cb6e5f0c2f/10.1177_20417314241291848-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/b8b266549608/10.1177_20417314241291848-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/9100efd117d1/10.1177_20417314241291848-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/1a61e5ecc557/10.1177_20417314241291848-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/69722a517be1/10.1177_20417314241291848-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/12c7636c2cc0/10.1177_20417314241291848-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/89256137970d/10.1177_20417314241291848-fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/2e1b993d993b/10.1177_20417314241291848-fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/56baa16110fe/10.1177_20417314241291848-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/a4ac5f8b4da3/10.1177_20417314241291848-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/29b64e2fecb0/10.1177_20417314241291848-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/bfae9172b94e/10.1177_20417314241291848-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/34cb6e5f0c2f/10.1177_20417314241291848-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/b8b266549608/10.1177_20417314241291848-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/9100efd117d1/10.1177_20417314241291848-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/1a61e5ecc557/10.1177_20417314241291848-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/69722a517be1/10.1177_20417314241291848-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/12c7636c2cc0/10.1177_20417314241291848-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/89256137970d/10.1177_20417314241291848-fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aa7/11536386/2e1b993d993b/10.1177_20417314241291848-fig12.jpg

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